Optical capture and isolation of circulating tumor cells in a micro-fluidic device utilizing size selective trapping with optical cogwheel tweezers

Abstract

Embodiments generally relate to devices, systems and methods for separating CTCs from blood cells using optical trapping, such as use of optical cogwheel tweezers. Through a pre-filtration process, using optical cogwheel tweezers, desired cells from a cell sample can be filtered from a relatively dilute sample. The filtered sample can then be analyzed by more precise means to determine overall concentrations from the original sample while maintaining cell viability.

What is claimed is: 
     
       1. A method of cell sorting, comprising:
 forming one or more optical cogwheel tweezers at a first position of a sample basin, the optical cogwheel tweezers having an aperture; 
 size-selectively filtering a biological sample, the filtering comprising:
 delivering a biological sample through the optical cogwheel tweezers at the first position, the biological sample comprising a cell sample, the optical cogwheel tweezers trapping a first portion of the cell sample from the biological sample and creating a first effluent, the first effluent being the remainder of the biological sample after removing the first portion of the cell sample; 
 directing the first effluent from the first position through an exhaust channel to an exhaust tank and the first portion of the cell sample through a sample channel using a flow control device in communication with the sample basin, a flow direction of the first effluent being parallel to a flow direction of the first portion of the cell sample; 
 directing coherent radiant energy at a point along the sample channel between the sample basin and a holding tank, the first portion of the cell sample providing fluorescence data in response to the coherent radiant energy; 
 separating the first portion of the cell sample into a secondary cell sample and a second effluent using the fluorescence data; 
 delivering the secondary cell sample to a holding tank; and 
 delivering the second effluent from the sample channel through an intermediate channel and the exhaust channel to the exhaust tank; and 
 
 repeating the size-selective filtering one or more times using the first effluent and the second effluent collected in exhaust tank. 
 
     
     
       2. The method of  claim 1 , further comprising detecting circulating tumor cells (CTCs), hemocytes and lymphocytes. 
     
     
       3. The method of  claim 2 , wherein the size selective filtering is repeated until the biological sample is clear of CTCs. 
     
     
       4. The method of  claim 1 , wherein the cell sample in the biological sample is tagged with a fluorophore. 
     
     
       5. The method of  claim 4 , wherein the fluorophore is conjugated to be selective for actively dividing cells. 
     
     
       6. The method of  claim 1 , wherein the aperture created by the optical cogwheel tweezers is between about 10 um and about 30 um wide. 
     
     
       7. The method of  claim 1 , wherein the biological sample is delivered at approximate in vivo rates. 
     
     
       8. The method of  claim 1 , wherein directing the first effluent to the exhaust channel and the first portion of the cell sample to the sample channel comprises:
 detecting the first portion of the cell sample at the first trap position; and 
 forming a first electric field and a second electric field in response to detecting the first portion, the first electric field positioned proximate an entrance to the exhaust channel and the second electric field positioned proximate an entrance to the sample channel, the second electric field being stronger than the first electric field. 
 
     
     
       9. The method of  claim 8 , wherein the first electric field is stronger than the second electric field in the presence of the first effluent.